A single aromatic core mutation converts a designed "primitive" protein from halophile to mesophile folding

Area of Science:

• Origin of Life Studies
• Biochemistry
• Evolutionary Biology

Background:

• The halophile environment is increasingly considered a potential "cradle" for early proteogenesis.
• A halophile-to-mesophile transition is hypothesized as a crucial step in early evolution.
• Aromatic amino acids are thought to be a late addition to the genetic code.

Purpose of the Study:

• To test if aromatic amino acids facilitated the halophile-to-mesophile transition through enhanced hydrophobic core-packing.
• To investigate the role of aromatic amino acids in early protein folding adaptation.

Main Methods:

• A "primitive" designed protein, using 10 prebiotic amino acids and requiring halophilic conditions for folding, was engineered.
• Aromatic amino acid substitutions were introduced into the core of this designed protein.
• The folding behavior of the modified protein under varying conditions was evaluated.

Main Results:

• A single aromatic amino acid substitution was sufficient to eliminate the need for halophilic conditions for protein folding.
• This suggests that aromatic amino acids significantly impact protein folding stability.
• The findings support the hypothesis of hydrophobic core-packing enhancement by aromatic amino acids.

Conclusions:

• The availability of aromatic amino acids likely facilitated a critical halophile-to-mesophile protein folding adaptation.
• This provides a selective advantage for the incorporation of aromatic amino acids into the genetic code.
• Aromatic amino acids played a key role in the transition from early halophilic to later mesophilic life.